High-throughput synthesis of nanoparticles using oscillating feedback microreactors: a selective scaling-out strategy

High-throughput synthesis of high-quality nanoparticles using traditional methods is difficult because of the complexities in controlling residence time and concentration. Passive oscillating feedback micromixers (OFMs) can overcome these difficulties. However, it remains a challenge to significantly increase throughput while retaining the microfluidic advantages. In this work, a selective scaling-out strategy was used to generate a series of enlarged OFMs, which were demonstrated to produce BaSO4 nanoparticles. A novel chaotic convection synthesis mode was found to produce high-quality BaSO4 nanoparticles (mean size, 24.91 nm; size distribution, 10–50 nm) at a high throughput of 281.4 mL min−1. The NP production rate can reach 538.4 g h−1, far exceeding the reported production rates.


SI-1 Oscillating Feedback Microreactor Fabrication
As shown in Fig. S1, the LSmicro2020 CNC engraving machine was used to carve the flow channel on a transparent PMMA plate with a processing speed of 22000 rpm, a feed rate of 35 mm/min, and a processing time of 2 h.Then the carved plate and a smooth cover plate were cleaned ultrasonically several times.After that, the two PMMA plates were placed in a vacuum-drying oven at a temperature of 80℃ for 30 min.The surfaces of the two dried PMMA plates were further treated in plasma with a plasma power of 170 W, vacuum pressure of 30mTorr, and treatment time of 30 s.
Then, the carved plate and the cover plate were immediately stacked together in the vacuum heat press LSmicro-nanoprint 100 for hot pressing bonding.The heating rate is 9℃/min, the hot pressing temperature is 115℃, the hot pressing pressure is 3 Bar, and the hot pressing time is 33 min.After hot pressing, the temperature was decreased at a cooling rate of 5℃/min.Finally, the pressing device was removed when the temperature was lowered to below 45℃, and a complete OFM was obtained. Laminar flow: Fig. S2(a) (Video S1) showed an ordered flow pattern at a very low throughput of Q R =0.5 mL/min (Re=16.94).A clear interface between the red and colorless liquids could be found, which was a typical feature of laminar flow.The two liquids pass directly through the OFM without any convection transverse to the main flow.And there was no feedback flow circulating through the feedback channels.In this case, it was predictable that NP synthesis was dominated by low-efficiency molecular diffusion, and the precipitation reaction was concentrated at the interface between the two liquids 1 .
 Vortex flow and feedback flow: As shown in Fig. S2(b) (Video S2), there was still a clear interface between the two phases as Q R increased to 2.0 mL/min (Re=67.76),but obvious secondary flows appeared.An obvious counterclockwise vortex formed on the colorless left side.Moreover, some red liquid entered the feedback channel and slowly circulated back to the mixing chamber.Such secondary flows of the vortex and the feedback flow became more noticeable when the Q R was further increased to 5.0 mL/min (Fig. S2(c) and Video S3) (Re=169.4).This case indicated that NPs could also be synthesized in the bulk phase of the two liquids, not only at the interface.The secondary flow, i.e., the convection transverse to the main flow could promote the mixing and mass transfer, which was beneficial for NP synthesis.However, the clear and straight interface throughout the whole OFM indicated that low-efficiency molecular diffusion was still a dominant factor for NP synthesis.
 Oscillating flow: When Q R was increased to 12.5 mL/min (Re=423.5),an oscillation occurred, as shown in Fig. S2(d ).The straight interface throughout the OFM was disrupted and feedback flows circulated rapidly through the feedback channels.In this case, the colors of all liquids in the OFM were essentially identical, indicating a sufficient mixing between the red and colorless liquids.The oscillating flow was popular for the high-throughput synthesis of NPs because of the efficient and rapid mixing and mass transfer rates with the high throughput 2 .

SI-3 Flow Patterns: Scaling Effects
The flow patterns essentially affect the mixing performance.Therefore, the effects of the scale-up on flow patterns were further investigated to determine the feasibility of scaled-out OFMs for high-throughput synthesis of NPs.All experimental conditions were the same as those described in Section SI-2 "Flow Pattern Classification".The laminar, vortex, and oscillating flows were also observed in the 2X～4X OFMs, but the scaling effects were noticeable.
 Laminar flow: As shown in Fig. S3(a) (Video S6-Video S9), the 1X～4X OFMs were all in laminar flow at Re=16.94.However, the mixing performance was affected by the enlargement ratio.In the 2X OFM～4X OFMs, the red deionized water phase diffused into the colorless Na 2 SO 4 phase.It could be concluded that the mass that transferred from the red water to the colorless Na 2 SO 4 phase was dominated by low-efficiency molecular diffusion since no secondary flow such as the vortex was observed.Furthermore, the larger the EF of the OFM, the larger the red water phase dispersion.This was because a long residence time was critical for increasing the diffusion mixing efficiency.This non-uniform mixing was not conducive to producing high-quality NPs with narrow particle size distribution, and therefore the laminar flow mode should be avoided in scaled-out OFMs.
 Vortex and feedback flow: As shown in Fig. S3(b) (Video S10-Video S13), the secondary flows such as vortex and partial feedback flows occurred in the 1X OFM at Re = 67.76,but the 4X OFM still maintained the laminar flow with a rather clear interface throughout the whole OFM.As for the 2X OFM, the vortex flow was only observed in the mixing chamber.When the OFM size was increased to 3X, there was no vortex and feedback flow to be observed.Compared with the 1X OFM, the mixing performance of the 2X～4X OFMs was inferior.Although the Re was the same, the velocity in the scaled-out OFMs was lower than that in the 1X OFM.The larger the size of the OFM, the lower the velocity near the exit of the OFM.Consequently, the mixing chamber could not generate sufficient pressure difference between both ends of the feedback channel to form the recirculating flow.The lower pressure difference between the Coanda step and the exit of the mixing chamber also could not generate a vortex.Therefore, the 2X～4X OFMs could not have excellent mixing performance.
 Circulating flow: As shown in Fig. S3(c) (Video S14-Video S17), the 1X～4X OFMs all generated an intense oscillating flow at Re of 960.1.The two phases were mixed relatively uniformly in the mixing chamber, but there was still a significant color difference between the left and right channels.In the 4X OFM, the oscillation frequency was lower than that of the 1X OFM, indicating a relatively poorer mixing performance.It could be seen that the depth of the red color on the left side of the 4X OFM was a little lighter than that on its right side.When the Re number was further increased to 3178, the colors of the two phases in the 1X～4X OFMs were almost identical, as shown in Fig. S3(d) (Video S18-Video S21).Here, complete mixing was achieved where the concentration was uniform everywhere and the residence time was rather short due to the high velocity at such high Re.The uniform concentration field and short residence time were essential for the synthesis of high-quality NPs.In this case, the scaling effects of the scaled-out OFMs could be neglected, making these OFMs ideal NP synthesizers.

SI-4 OFM without feedback channels
Fig. S4 shows the structure of the 2X OFM without feedback channels.Except for the feedback channels, the other structure is the same as the 2X OFM.

SI-5 Measurement of BaSO 4 NP Production Rate and Yield
As shown in Fig. S5, set the concentration ratio of BaCl 2 and Na 2 SO 4 to maintain 1:1 at all times and change the concentrations to 0.1, 0.15, 0.2, 0.25, and 0.3 moL/L.The flow rates of the two phases were both 140.7 mL/min (the total flow rate was 281.4 mL/min), and the volumes of BaCl 2 and Na 2 SO 4 solutions were both 10 mL (the total volume of reactant solutions, V total =20mL).The two reactant solutions were fed into the 4X OFM.A bottle containing 200 mL of deionized water was placed at the outlet of the 4X OFM to collect NPs.The amount of deionized water was much higher than the amount of reactants so the unreacted reactants were sufficiently diluted in the collection bottle.As a result, the reaction between unreacted BaCl 2 and Na 2 SO 4 coming out of the OFM could be neglected.Namely, the NP synthesis reaction could be quenched in the collection bottle so as not to affect the yield and production rate measurement of NPs generated within the OFM.Then, the collected product solution in the bottle was immediately centrifuged (8000 rpm, 1 min) to obtain wet BaSO 4 NPs (Quality M c , g).The collected NPs were washed once with water and twice with anhydrous ethanol, and the wet NPs were further dried to obtain white NPs (50 °C, 24 h).As a result, the actual NP production rate and yield could be determined by the following equations.BaSO 4 NP production rate (g/h)=M c /(V total /Q total ) *60 (Eq.S1) BaSO 4 NP yield (%)=M c /M i *100% (Eq.S2) Where V total =20 mL and Q total =281.4mL/min.M c is the quality (g) of the dried BaSO 4 NPs collected in the bottle.M i is the theoretical generation quality (g) of BaSO 4 NPs when BaCl 2 and Na 2 SO 4 react completely.Table S3 shows the result of production rates and yields at different reactant concentrations.

Screenshots Of Movie Clips
The

Fig. S1
Fig. S1 Manufacturing process diagram of OFM ) and Fig. S2(e) (Video S4).In Fig. S2(d), the interface deviated to the right side and immediately began to deviate to the left (Fig. S2(e)), which produced an oscillation.Fig. S2(f) (Video S5) showed a more intense oscillating flow at Q R =28.3 mL/min (Re=960.1

Fig. S3
Fig. S3 Effects of the enlargement factor EF and Reynolds number on flow patterns in

Fig. S5
Fig. S5 Morphologies and size distributions of NPs synthesized in 4X OFM with
images below are screenshots of Movie clips.Video S1 Movie of flow pattern in 1X OFM: Q R = Q L = 0.5 mL/min: stable laminar flow (it seems to be stationary) Video S2 Movie of flow pattern in 1X OFM: Q R = Q L = 2 mL/min: vortex flow and

Table S1
Comparison between OFM reactor and other reactors in terms of throughput.

Table S2
Original data of nanoparticle size distribution obtained from TEM images in TableS3The NP production rates and yields in 4X OFM with different concentrations (total throughput, 281.4mL/min;Re=3178)